PROJECT SUMMARY The Washington University Pancreatic Cancer Specialized Program of Research Excellence (SPORE) is a highly translational cancer research program focused entirely on the deadliest form of the disease, pancreatic ductal adenocarcinoma (PDAC). Our outstanding investigators have complementary expertise in basic and clinical sciences, and our teams leverage individual expertise in immunology, drug development, genomics, and imaging to develop novel diagnostic and therapeutic approaches to PDAC. This SPORE includes four research projects, an administrative core, two shared-resources cores, and developmental research and career enhancement programs. With the help of our External and Internal Advisory Boards, we have intentionally selected the projects that have the greatest potential to impact PDAC. All four of our selected projects include a therapeutic trial, and two take advantage of immunologic discoveries made at WU. We have two projects that utilize small molecule inhibitors of pathways that are known to be active in PDAC. The four projects in our application are designed to have significant potential to change clinical practice within five years. Project 1: Overcoming Tumor-Induced Immune Suppression to Improve Responses to Immunotherapy Project 2: Clinical Development of the Pancreatic Cancer Drug Conjugate SW V-49 Project 3: Combination Inhibition of ERK for Pancreatic Cancer Treatment Project 4: Translation and Preclinical Studies of a Personalized Pancreatic Cancer Vaccine Our long-term goal is to improve survival of patients diagnosed with PDAC. To achieve this, we will promote institutional and inter-institutional collaborative science, with an emphasis on translation. We expect that no singular approach will solve PDAC, and fully commit to supporting the development of novel ideas and young investigators. Our SPORE will provide access to pancreatic cancer-specific resources to facilitate this mission.